20.1a History of DNA and Structure Cell Division, Genetics, Molecular Biology

DNA Deoxyribonucleic acid (DNA) Found in nucleus of all organisms (within chromosomes) DNA only molecule capable of replicating itself Contains instructions that ensure continuity of life - coded within chemical messages of DNA - regulates the production of proteins Ability to change due to mutations and new combinations of genes

Frederich Miescher 1869 – extracted viscous white substance from bandages of wounded soldiers - slightly acidic, phosphorus & nitrogen rich - called it nuclein Nuclein composed of acidic portion (nucleic acid) and alkaline portion (protein) Single nucleic acid was later shown to be 2 nucleic acids - deoxyribonucleic acid (DNA) - ribonucleic acid (RNA) DNA material of heredity: early focus was on proteins

Joachim Hammerling Acetabularia: green algae, 3 distinct regions (cap, stalk, foot) Nucleus in foot: cut off cap and new cap regenerated, cut off foot, no new foot regeneration Suggested hereditary material located in nucleus

Frederick Griffith Lab Exercise pg 644 Streptococcus pneumoniae – 2 forms - virulent: S-form (coated) - harmless: R-form S-form cells heated and killed, injected into mice and they lived Heated cells mixed with R-form cells, killed mice Concluded there must be something chemical altering the living cells: transformation - transformed into virulent cells

Avery, McCarty, MacLeod Lab Exercise pg – experiments with Streptococcus pneumoniae in test tubes Treated heat-killed virulent bacteria with a protein- destroying enzyme: transformation still occurred Treated heat-killed virulent bacteria with DNA-destroying enzyme: transformation DID NOT occur Concluded DNA was “transforming principle” - likely source of hereditary information

Alfred Hershey & Martha Chase 1952 – used bacteriophages (virus) that infect bacterial host (2 components: DNA and protein coat) Infects by injecting DNA into it, virus multiplies within and then bursts out, killing the cell Hershey & Chase concluded that only the DNA, not protein coat, enters bacteria - tagged viral proteins with isotope of sulfur (not component of DNA) - tagged viral DNA with isotope of phosphorus (component of DNA) Allowed tagged bacteriophage to infect bacterial cell Cells blended to remove protein coats and centrifuged to isolate virus from bacteria

Bacterial cells found to contain isotope of phosphorus, not isotope of sulfur Isotope of sulfur found in culture medium Conclusion! DNA was hereditary material

James Watson & Francis Crick Known that DNA comprised of chains of nucleotides - consist of 5-carbon cyclic ring: deoxyribose sugar - one of 4 nitrogenous bases attached to 1’ carbon - phosphate group attached to 5’ carbon 4 bases: adenine (A), guanine (G), thymine (T), cytosine (C) - A & G: purines (double ring) - C & T: pyrimidines (single ring) Evidence from Edwin Chargaff: calculated that amount of adenine always equal to amount of thymine (same for guanine and cytosine). Observed for almost all species Evidence from Rosalind Franklin: x-ray diffraction, photograph taken - shows that DNA was a helix, likely double-stranded

James Watson & Francis Crick All the evidence compiled, Watson & Crick created a 3D model Portrayed relationship between bases as well as bond angles and spacing of atoms - consistent with observations from other researchers to that point Won Nobel Prize in 1962 along with Maurice Wilkins (researcher in charge of Rosalind Franklin’s work) Rosalind Franklin left out – she died prior to 1962

DNA Structure 2 strands of nucleotides Each nucleotide contains: - deoxyribose sugar - phosphate group - nitrogenous base Covalently bonded into double helix like a twister ladder - hydrogen bonds keep helix together Base pairs are rungs, sugar/phosphate backbones are struts Complementary base pairing to form rungs - A pairs with T - C pairs with G

DNA Structure

Opposite strand always have the complementary sequence of bases 5’ – ATGCCGTTA – 3’ 3’ – TACGGCAAT – 5’ Antiparallel: run parallel but in opposite directions - one strand has 5’ carbon & phosphate group at one end and 3’ carbon & hydroxyl group of deoxyribose sugar at other end - other strand runs opposite 3’ to 5’ Direction important to enzymes interacting with DNA - only read or copy DNA in one direction DNA Structure

Nobel Prize - DNA